1. Field of the Invention
This application is a 371 of PCT/EP97/01581 filed Mar. 27, 1997.
The invention relates to processes for the stabilization and dispersion of vegetable oils comprising polyunsaturated fatty acid radicals by means of .gamma.-cyclo-dextrin, to the complexes thus prepared, and to their use.
2. The Prior Art
Cyclodextrins are cyclic oligosaccharides which consist of 6, 7 or 8 .alpha.(1-4)-linked anhydroglucose units. The .alpha.-, .beta.- or .gamma.-cyclodextrins, which are prepared by, for example, enzymatic starch conversion, differ in the diameter of their hydrophobic cavity and are generally suitable for the inclusion of a large number of lipophilic substances.
Vegetable oils consist predominantly of simple and mixed triacylglycerols, composed of saturated, monounsaturated or polyunsaturated natural fatty acid radicals with chain lengths of less than or equal to 18 carbon atoms which are esterified with glycerol.
Vegetable oils with a high proportion of triacylglycerols containing polyunsaturated fatty acids are valuable substances whose skin care properties are exploited in cosmetics. In addition, they are employed in the food sector to provide essential fatty acids.
The main problem for the wider use of these oils is their sensitivity to atmospheric oxygen, heat and microorganisms, in particular with exposure to light, peroxides being formed (autoxidation of the unsaturated fatty acid radical). Autoxidation takes place at the C--C double bond, which primarily leads to the formation of peroxides and then to aldehydes, ketones and acids. Secondary reactions involve isomerizations and polymerizations.
The peroxide content, expressed by the peroxide number (PON), is the decisive quality criterion for vegetable oils. Oils with a high peroxide number smell rancid and cannot be used for applications. The peroxide number provides information on the progressive oxidation process, or the amount of lipid peroxides. Changes in color and odor are other characteristics for destabilization of the vegetable oils.
The peroxides formed by destabilization of the unsaturated triacylglyerols increase the undesired toxic potential of the formulations. Also, a series of cosmetically desirable effects are reduced or even eliminated by the destabilization: the following may be mentioned by way of example:
The polyunsaturated fatty acids such as, for example, linoleic acid and gamma-linolenic acid, cause an increased elasticity of the skin by forming mobile and flexible structures in the cell membranes or skin lipids by means of their elbow configuration (C--C double bonds with cis configuration). A high proportion of poly-unsaturated fatty acids leads to a higher packing density of the skin lipids, and this results in an improved barrier function of the skin, which, in turn, leads to reduced transepidermal water loss. Cell proliferation is increased. Autoxidation lowers the number of C--C double bonds and thus the number of the structures responsible for mobility and flexibility.
Apart from the use of oils containing unsaturated triacylglycerols in cosmetics, the topical or oral administration as medicament or as synthetic food may also be mentioned. Certain unsaturated fatty acids such as, for example, linoleic acid or gamma-linolenic acid are absolutely necessary, i.e. esssential, for the mammalian organism since they cannot be synthesized by the latter and must therefore be administered externally.
The following measures are known from the prior art to stabilize, by means of cyclodextrin, vegetable oils containing polyunsaturated fatty acids:
CA:107:22242k describes a cholesterol-lowering foodstuff in which .gamma.-linolenic acid is formulated with .alpha.-cyclodextrin.
Milk or powdered milk containing .beta.-cyclodextrin complexes of triacylglycerols with a proportion of 70% of .gamma.-linolenic acid are known from CA:107:133049x.
CA:87:116647s describes cyclodextrin inclusion compounds of .alpha.- and .beta.-cyclodextrin with mono-, di- and triacylglycerols exemplified by soybean oil.
In CA:108:220598, it is found that storage of a triacylglycerol/.beta.-cyclodextrin complex at 40.degree. C. for one month results in an over 50% reduced peroxide formation in comparison with non-complexed triacylglycerol.
Chemical Abstract CA:108:192767y describes the stabilization of .gamma.-linolenic acid in evening primrose oil by inclusion into .beta.-cyclodextrin.
In CA:113:217812, .beta.-cyclodextrin is employed for improving the emulsion properties of fatty acids in skin cosmetic formulations.
Chemical Abstract CA: 107:46327t describes therapeutic beverages which comprise a .beta.-cyclodextrin complex of .gamma.-linolenic acid.
Journal of Inclusion Phenomena and Molecular Recognition in Chemistry 16 (1993), pp. 339-354, proves the stabilization of linseed oil as .alpha.- and .beta.-cyclodextrin complexes in comparison with free oil by the uptake of oxygen in a Warburg apparatus. The use of .alpha.-cyclodextrin is disclosed as being especially preferred in this publication. The authors suggest on p. 342, 3rd paragraph from the bottom, that the linear fatty acids, both free and in the form of their glycerol esters, form the most stable complexes with .alpha.-cyclodextrin, which is the cyclodextrin with the smallest cavity.